Cardiac dysfunction in patients with cirrhosis and acute decompensation.

The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%-70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute-on-chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research.

Effect of beta-blockers on multiple haemodynamics in cirrhosis: A cross-over study by MR-imaging and hepatic vein catheterization.

BACKGROUND: Non-selective beta-blockers (NSBB) are widely used in the treatment of patients with cirrhosis. Only about 50% respond with a sufficient reduction in their hepatic venous pressure gradient (HVPG) and NSBB may induce detrimental cardiac and renal effects in the presence of severe decompensation. We aimed to assess the effects of NSBB on haemodynamics using magnetic resonance imaging (MRI) and to assess if these haemodynamic changes were related to the disease severity and HVPG response. METHOD: A prospective cross-over study of 39 patients with cirrhosis. Patients underwent hepatic vein catheterization and MRI with assessments of HVPG, cardiac function, systemic and splanchnic haemodynamics before and after propranolol infusion. RESULTS: Propranolol induced significant decreases in cardiac output (-12%) and blood flow of all vascular compartments, with the largest reductions seen in the azygos venous (-28%), portal venous (-21%), splenic (-19%) and superior mesenteric artery (-16%) blood flow. Renal artery blood flow fell by -5% in the total cohort, with a more pronounced reduction in patients without ascites than in those with ascites (-8% vs. -3%, p = .01). Twenty-four patients were NSBB responders. Their changes in HVPG after NSBB were not significantly associated with other haemodynamic changes. CONCLUSION: The changes in cardiac, systemic and splanchnic haemodynamics did not differ between NSBB responders and non-responders. The effects of acute NSBB blockade on renal flow seem to depend on the severity of the hyperdynamic state, with the largest reduction in renal blood flow in compensated patients compared to decompensated patients with cirrhosis. However, future studies are needed to assess the effects of NSBB on haemodynamics and renal blood flow in patients with diuretic-resistant ascites.

Cardiovascular Mapping in Cirrhosis From the Compensated Stage to Hepatorenal Syndrome: A Magnetic Resonance Study.

INTRODUCTION: Arterial vasodilation and hyperdynamic circulation are considered hallmarks of the pathophysiological mechanisms of decompensation in cirrhosis. However, detailed characterization of peripheral, splanchnic, renal, and cardiac hemodynamic have not previously been published in a spectrum from healthy stage to advanced decompensated liver disease with hepatorenal syndrome-acute kidney injury (HRS-AKI). METHODS: We included 87 patients with cirrhosis and 27 healthy controls in this prospective cohort study. The population comprised patients with compensated cirrhosis (n = 27) and decompensated cirrhosis (n = 60); patients with decompensated cirrhosis were further separated into subsets of responsive ascites (33), refractory ascites (n = 16), and HRS-AKI (n = 11). We measured portal pressure and assessed regional blood flow by magnetic resonance imaging. RESULTS: Patients with compensated cirrhosis experienced higher azygos venous flow and higher hepatic artery flow fraction of cardiac index than controls ( P < 0.01), but other flow parameters were not significantly different. Patients with decompensated cirrhosis experienced significantly higher cardiac index ( P < 0.01), higher superior mesenteric artery flow ( P = 0.01), and lower systemic vascular resistance ( P < 0.001) compared with patients with compensated cirrhosis. Patients with HRS-AKI had the highest cardiac output and lowest renal flow of all groups ( P < 0.01 and P = 0.02, respectively). Associations of single hemodynamic parameters were stronger with model for end-stage liver disease than with portal pressure. DISCUSSION: The regional cardiocirculatory changes seem closely linked to clinical symptoms with 3 distinguished hemodynamic stages from compensated to decompensated cirrhosis and, finally, to HRS-AKI. The attenuated renal perfusion despite high cardiac output in patients with HRS-AKI challenges the prevailing pathophysiological hypothesis of cardiac dysfunction as a causal factor in HRS-AKI. Finally, magnetic resonance imaging seems an accurate and reliable noninvasive method to assess hemodynamics and has potential as a diagnostic tool in patients with cirrhosis.

Dipeptidyl peptidase-3 is associated with severity of liver disease and circulatory complications in patients with cirrhosis.

BACKGROUND: Patients with cirrhosis suffer from a complex multiorgan disturbance and their prognosis is influenced by the development of portal hypertension and systemic circulatory dysfunction. Although non-invasive techniques such as transient elastography aid in early detection, there is an unmet need for reliable markers of these clinically significant complications. METHODS: We conducted an exploratory single-center study investigating dipeptidyl peptidase-3 (DPP3) concentrations in various vascular beds in a cohort of 48 patients with cirrhosis and 16 healthy controls. Liver vein catheterisation with sampling from femoral artery and femoral, renal and hepatic veins as well as measurement of hepatic pressure and liver function via indocyanine green and galactose elimination tests were performed. RESULTS: DPP3 concentrations were higher in cirrhotic patients compared to controls (12.6 vs. 7.4 ng/mL, p = 0.006) and increased according to the severity of cirrhosis. DPP3 associated with MELD-Na score, Child class, indocyanine green clearance, increased DPP3 with the increased hepatic venous pressure gradient (p = 0.015) as well as increased heart rate and reduced systemic vascular resistance. DPP3 concentrations predicted the presence of clinically significant portal hypertension in cirrhotic patients (AUROC 0.78, 95% CI 0.65-0.9). CONCLUSION: DPP3 is a promising marker for portal hypertension and systemic hemodynamic changes in cirrhosis.

Dobutamine reverses the cardio-suppressive effects of terlipressin without improving renal function in cirrhosis and ascites: a randomized controlled trial.

Acute kidney injury and hepatorenal syndrome (HRS) are frequent complications in patients with cirrhosis and ascites. First-line treatment is terlipressin, which reverses HRS in ~40% of patients but also lowers cardiac output (CO). We aimed to investigate whether reversing the cardio-suppressive effect of terlipressin with the ß-adrenoceptor agonist dobutamine would increase CO and thereby increase the glomerular filtration rate (GFR). We randomized 25 patients with cirrhosis, ascites, and impaired renal function (2:2:1): group A received terlipressin followed by the addition of dobutamine; group B received dobutamine and terlipressin as monotherapies; and group C received placebo. Renal and cardiac functions were assessed during 8 clearance periods of 30 min, and concentrations of vasoactive hormones were measured. Dobutamine as a monotherapy increased CO (1.03 L/min, P < 0.01) but had no significant effects on GFR. Renin (P < 0.05), angiotensin II (P < 0.005), and aldosterone (P < 0.05) increased after dobutamine infusion. Terlipressin as a monotherapy improved GFR (18.9 mL·min-1·m-2, P = 0.005) and mean arterial pressure (MAP) (14 mmHg, P = 0.001) but reduced CO (-0.92 L/min, P < 0.005) and renin (P < .005). A combined treatment of dobutamine and terlipressin had a positive effect on CO (1.19 L/min, P < 0.05) and increased renin (P < 0.005), angiotensin II (P < 0.005), and aldosterone (P < 0.05), but it had no significant effects on MAP or GFR. Dobutamine reversed the cardio-suppressive effect of terlipressin in cirrhosis, ascites, and impaired renal function. However, dobutamine reduced peripheral vascular resistance, activated renin-angiotensin-aldosterone system, and did not improve GFR compared with terlipressin as a monotherapy. Therefore, dobutamine cannot be recommended in cirrhosis and ascites.NEW & NOTEWORTHY This study shows that the cardio-suppressive effects of the vasopressin receptor agonist terlipressin can be reversed by dobutamine. This is a novel observation in patients with decompensated cirrhosis. Furthermore, we show that dobutamine reduced the peripheral vascular resistance and activated the renin-angiotensin system, whereas renal function was not further improved by terlipressin alone.

Cardiac dysfunction in cirrhosis: a 2-yr longitudinal follow-up study using advanced cardiac imaging.

The temporal relationship between cirrhotic cardiomyopathy, progression of liver disease, and survival remains unknown. Our aim was to investigate the development of structural and functional cardiac changes over time with the progression of cirrhosis and outcome. Sixty-three cirrhotic outpatients (Child class: A = 9, B = 46, C = 8) and 14 healthy controls were included in this 2-yr longitudinal study. Advanced cardiac characteristics such as cardiac MRI with extracellular volume (ECV) quantification, speckle tracking echocardiography, and biomarkers were assessed at 0/6/12/18/24 mo. Patients were followed-up for a median of 30 mo with registration of acute decompensations (ADs), liver transplantations (LTs), and deaths. Patients who progressed, underwent LT or died had more pronounced cardiac dysfunction, structural myocardial changes, and left atrial enlargement. Conversely, limited cardiac deterioration was seen in patients who remained stable or improved in cirrhosis. During follow-up 25 patients developed AD, 4 underwent LT, and 20 died. Mean arterial pressure was the only cardiovascular parameter associated with death in a univariate analysis (P = 0.037), and the main predictors were model for end-stage liver disease and age. However, last-visit myocardial ECV was independently associated with the combined end point of LT/death (P = 0.001), and in patients with AD a low cardiac index was independently associated with death (P = 0.01). Cardiac function seems to deteriorate with the progression of cirrhosis and affects prognosis, especially in patients with AD. Conversely, patients with stable cirrhosis have limited progression in cardiac dysfunction over a 2-yr period with modest impact on survival. The results encourage careful cardiac monitoring in advanced cirrhosis.NEW & NOTEWORTHY For the first time, we have performed advanced cardiac imaging to investigate the development of cirrhotic cardiomyopathy over 2 years. We show that cardiac dysfunction deteriorates with progression of cirrhosis and may affect the prognosis in patients developing acute decompensation. Especially, structural myocardial abnormalities, left atrial enlargement, and a hypodynamic cardiac state seem of importance. Conversely, limited cardiac progression is seen in stable cirrhosis. These findings provide new insight into our understanding of cirrhotic cardiomyopathy.

Myocardial extracellular volume quantified by magnetic resonance is increased in cirrhosis and related to poor outcome.

BACKGROUND & AIMS: The underlying pathogenesis of cirrhotic cardiomyopathy remains unclear. Structural myocardial changes including diffuse fibrosis may be involved and can be accurately assessed by cardiac MRI (CMR) with quantification of the extracellular volume (ECV).This is the first application of this technique in patients with cirrhosis. We aimed to investigate the presence of diffuse myocardial fibrosis and to determine the relation to disease severity, cardiac function and outcome. METHODS: A prospective study including 52 cirrhotic patients and 10 healthy controls. All patients underwent CMR with ECV quantification, tissue Doppler echocardiography, and biochemical assessments. Patients were followed up for a median of 25 months with registration of death and liver transplantation (LT). RESULTS: Myocardial ECV was higher in the patients compared with healthy controls (31.2 ± 6 vs 27.4 ± 3%, P = .04). Furthermore, ECV increased across the Child Pugh A/B/C classes (26.9 ± 4/31.5 ± 5/34.4 ± 6%, P = .02). Four-teen patients experienced the composite end-point of death/LT during follow-up and these patients had higher ECV (33.2 ± 4 vs 30.4 ± 6%, P = .04). In a univariate Cox regression analysis ECV was associated with poor transplant-free survival (HR 3.6 [1.1-11.6]; P = .03). However, MELD and CRP remained the strongest predictors in a multivariate analysis. ECV correlated with cardiac index (r = 0.44, P = .001), CRP (r = 0.46, P = .001), proANP (r = 0.50, P < .001), and proBNP (r = 0.40, P = .005). CONCLUSIONS: Myocardial ECV is increased in patients with cirrhosis and seems related to disease severity and transplant-free survival. These changes most likely reflect subclinical diffuse myocardial fibrosis and may represent a structural element of cirrhotic cardiomyopathy.

Low ascitic fluid total protein levels is not associated to the development of spontaneous bacterial peritonitis in a cohort of 274 patients with cirrhosis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a complication to decompensated cirrhosis. Fluoroquinolones may prevent SBP. However, predictive markers for SBP are wanted. Guidelines suggest that patients with ascitic fluid protein below 15 g/l receive fluoroquinolones to prevent SBP. This study aimed to assess the clinical utility of low ascitic fluid protein in predicting SBP in patients with cirrhosis and ascites. METHODS: A total of 274 patients with cirrhosis and ascites underwent paracentesis between January 2010 and June 2015. Patients were followed until two years, development of SBP, initiation of ciprofloxacin, death or liver transplantation. Data were compared between groups of patients with 'high' or 'low' ascitic protein. RESULTS: SBP developed in 31 patients (11.3%). No difference in mean ascitic fluid protein levels were found (SBP, mean: 8.5 g/l and no SBP 8.2 g/l, p = .825). SBP developed at equal rates in patients with 'high' or 'low' ascitic protein (10.8% (≤15 g/l) and 14.0% (>15 g/l), p = .599). The same trend was observed when adjusting the threshold below 10 g/l (11.9% (≤10 g/l) and 10.2% (>10 g/l), p = .697). CONCLUSIONS: Low ascitic fluid protein does not predict SBP in patients with cirrhosis and ascites. Better markers are needed.

Pronounced Coronary Arteriosclerosis in Cirrhosis: Influence on Cardiac Function and Survival?

BACKGROUND: The relation between excessive alcohol consumption and coronary arteriosclerosis has remained controversial. The etiology of cirrhosis has been considered a substantial risk factor for development of arteriosclerotic lesions. The coronary artery calcium-score derived from coronary CT angiography is a robust marker of coronary arteriosclerosis. AIMS: To study the burden of coronary arteriosclerosis in cirrhotic patients of various etiologies and association to cardiac dysfunction and survival. METHODS: Fifty-seven patients with cirrhosis without cardiovascular disease underwent coronary CT angiography, tissue Doppler echocardiography, electrocardiogram and registration of clinical and biochemical characteristics. RESULTS: In patients with cirrhosis the median coronary artery calcium-score was increased in comparison with age and race-adjusted healthy reference values (men: 328 vs. 9 HU and women: 136 vs. 0 HU; p < 0.001). Moreover, the coronary artery calcium-score in alcohol-related cirrhosis was significantly higher than in nonalcohol-related cirrhosis (362 vs. 46 HU, p < 0.001). Coronary artery calcium-score correlated with age (p = 0.002) but not with established cardiovascular risk factors including smoking, type 2 diabetes, hypertension, gender, or hypercholesterolemia. Coronary artery calcium-score was associated with diastolic dysfunction, lateral e´ (p = 0.025), but not with other markers of cardiac dysfunction. During a median follow-up of 25 months 12 patients (21%) died but coronary artery calcium-score was not associated with survival. CONCLUSIONS: Coronary arteriosclerosis was particular extensive in patients with alcoholic cirrhosis. However, the current results suggest that coronary arteriosclerosis only have limited influence on cardiac function and survival. Surprisingly, no other established risk factors apart from age seemed to interfere with coronary arteriosclerosis in cirrhotic patients.

Bile acids and cardiovascular function in cirrhosis.

Cirrhotic cardiomyopathy and the hyperdynamic syndrome are clinically important complications of cirrhosis, but their exact pathogenesis is still partly unknown. Experimental models have proven the cardiotoxic effects of bile acids and recent studies of their varied receptor-mediated functions offer new insight into their involvement in cardiovascular dysfunction in cirrhosis. Bile acid receptors such as farnesoid X-activated receptor and TGR5 are currently under investigation as potential therapeutic targets in a variety of pathological conditions. These receptors have also recently been identified in cardiomyocytes, vascular endothelial cells and smooth muscle cells where they seem to play an important role in cellular metabolism. Chronic cholestasis leading to abnormal levels of circulating bile acids alters the normal signalling pathways and contributes to the development of profound cardiovascular disturbances. This review summarizes the evidence regarding the role of bile acids and their receptors in the generation of cardiovascular dysfunction in cirrhosis.

Diastolic dysfunction in cirrhosis.

Development of esophageal varices, ascites, and hepatic nephropathy is among the major complications of cirrhosis. The presence of cirrhotic cardiomyopathy, which includes a left ventricular diastolic dysfunction (DD), seems to deteriorate the course of the disease and the prognosis. Increased stiffness of the cirrhotic heart may decrease the compliance and result in DD. The prevalence of DD in cirrhotic patients averages about 50 %. It can be evaluated by transmitral Doppler echocardiography, tissue Doppler echocardiography, and cardiac magnetic resonance imaging. There seems to be a relation between DD and the severity of liver dysfunction and the presence of ascites. After liver transplantation, DD worsens the prognosis and increases the risk of graft rejection, but DD improves after few months. Insertion of a transjugular intrahepatic portosystemic shunt increases left ventricular diastolic volumes, and DD is a predictor of poorer survival in these patients. Future studies should aim at disclosing pathophysiological mechanisms behind the developing of DD in cirrhosis in relation to patient characteristics, development of complications, treatment, and risk associated with interventional procedures.

Cardiac and proinflammatory markers predict prognosis in cirrhosis.

BACKGROUND & AIMS: Inflammation and cardiac dysfunction plays an important role in the development of complications leading to increased mortality in patients with cirrhosis. Novel cardiac markers such as prohormone of ANP (proANP), copeptin and high-sensitivity troponin T (hs-TnT) and proinflammatory markers including soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP) are related to these complications. We aimed to investigate if cardiac and proinflammatory markers are related to severity of liver disease, cardiac and haemodynamic changes, and long-term survival. METHODS: One hundred and ninety-three stable cirrhotic patients (Child class: A = 46; B = 97; C = 50) had a full haemodynamic investigation performed with measurement of splanchnic and systemic haemodynamics and measurement of circulating levels of proBNP, proANP, copeptin, hs-TnT, LBP, IL 6, IL 8, IP 10, VEGF, hs-CRP and suPAR. RESULTS: Soluble urokinase-type plasminogen activator receptor soluble urokinase-type plasminogen activator receptor, hs-CRP, and hs-TnT were significantly different throughout the Child classes (P < 0.01; P < 0.01; P < 0.02). All markers except copeptin correlated with indicators of disease severity in cirrhosis; ProANP and suPAR correlated with hepatic venous pressure gradient (r = 0.24 and r = 0.34; P < 0.001) and systemic vascular resistance (r = -0.24 and r = -0.33; P < 0.001). Cardiac (proANP, hs-TnT; P < 0.01) and proinflammatory (hs-CRP, suPAR; P < 0.05) markers were associated with mortality in a univariate Cox analysis, however, the strongest predictors of mortality in a multivariate Cox analysis were hs-TnT, ascites and hepatic venous pressure gradient (reg.coeff.: 0.34, P < 0.001; 0.16, P < 0.001; 0.06, P = 0.04). CONCLUSION: Markers of cardiac dysfunction and inflammation are significantly associated with disease severity, degree of portal hypertension and survival in cirrhosis. In particular, hs-TnT and suPAR seem to contain prognostic information.

Association of low mechano-energetic efficiency and prognosis in liver cirrhosis.

BACKGROUND: In cirrhosis, cardiac systolic dysfunction as part of cirrhotic cardiomyopathy affects prognosis. Myocardial mechano-energetic efficiency (MEE) is an estimate of left ventricular performance. In this study we investigated the relation of MEE to patient characteristics and its impact on survival in patients with cirrhosis. PATIENTS AND METHODS: We included 283 patients with cirrhosis of different severity according to the Child-Pugh classifications (A/B/C: 106/87/90). All patients had a liver vein catheterization and a hemodynamic investigation performed including determination of cardiac output (CO), stroke volume and heart rate (HR). These data were used to assess MEE, which was defined as (stroke volume/HR) × 1.666. RESULTS: Eighty-nine percent of patients had portal hypertension (hepatic venous pressure gradient >5 mmHg) and 80% indications of hyperdynamic circulatory state (increased CO and HR). There was no difference in MEE in Child-Pugh class C patients (2.03) versus Child-Pugh class A (1.98) and B (2.05) patients. In Child-Pugh class C patients, low MEE was associated with a poorer prognosis. CONCLUSION: In our study, MEE does not seem to be associated with severity of the liver disease, but in patients with advanced disease low MEE is associated with a poorer prognosis. The prognostic impact of MEE should be further investigated.

How non-alcoholic fatty liver disease and cirrhosis affect the heart.

Liver diseases affect the heart and the vascular system. Cardiovascular complications appear to be a leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis. The predominant histological changes in the liver range from steatosis to fibrosis to cirrhosis, which can each affect the cardiovascular system differently. Patients with cirrhotic cardiomyopathy (CCM) and NAFLD are at increased risk of impaired systolic and diastolic dysfunction and for suffering major cardiovascular events. However, the pathophysiological mechanisms behind these risks differ depending on the nature of the liver disease. Accurate assessment of symptoms by contemporary diagnostic modalities is essential for identifying patients at risk, for evaluating candidates for treatment, and prior to any invasive procedures. This review explores current perspectives within this field.

Altered serum bile acid composition is associated with cardiac dysfunction in cirrhosis.

BACKGROUND: Elevated serum bile acids (BA) are harmful to the heart and alterations in the BA composition have been suggested to cause cardiovascular disturbances in cirrhosis. AIM: To investigate any associations between specific groups or individual serum BA and structural and functional cardiac abnormalities in patients with cirrhosis. METHODS: An explorative study in 86 patients with cirrhosis. All participants underwent extensive cardiac assessment, including cardiac MRI with quantification of myocardial extracellular volume (ECV), which is indicative of diffuse myocardial fibrosis. A panel of 15 individual serum BA and C4, a marker of de novo bile acid synthesis, were assessed. RESULTS: Patients with advanced cirrhosis had higher levels of total BA and conjugated BA, as well as lower C4 levels (p < 0.001). Conjugated BA levels were higher in patients with a high cardiac index (p < 0.001), increased left atrial volume index (LAVI) (p < 0.001), and in those with an abnormal myocardial ECV (p < 0.05). We also found several strong correlations between conjugated BA, both as a group and individually, and parameters of cardiac dysfunction. In a model adjusted for sex, age, BMI and MELD, conjugated BA remained significantly associated with LAVI, septal e', left ventricular volumes and cardiac index. In addition, taurocholic acid correlated closely with hepatic venous pressure gradient (HVPG) (p = 0.01). CONCLUSIONS: Increased serum concentrations of conjugated BA are associated with several cardiac parameters, indicating a potential role in the development of hyperdynamic circulation and cardiac dysfunction in cirrhosis. Moreover, taurine-conjugated BA are associated with portal hypertension.

Peptidylglycine α-amidating monooxygenase and adrenomedullin measurement in patients with hepatic cirrhosis.

Background: Peptidylglycine α-amidating monooxygenase (PAM) is an enzyme involved in the maturation of regulatory peptides. Here we examined PAM activity and adrenomedullin (bio-ADM) concentrations in patients with hepatic cirrhosis and determined net changes across the liver, kidneys and leg. Materials & methods: A total of 48 patients with hepatic cirrhosis and 16 control subjects were included. All patients and controls underwent an invasive procedure with blood collected across organs. Results: PAM activity was increased in cirrhotic patients but without a net change across the liver, leg or kidney. In contrast, bio-ADM concentrations were associated with severity of disease and found to be higher in venous blood from the liver. Conclusion: Increased PAM activity in patients with hepatic cirrhosis may reflect other organs involved in cirrhotic disease.

Severe liver disease is a life-threatening condition that affects people all over the world. To improve doctors' ability to diagnose the disease and to follow the disease as it progresses, there is a need for new tools. Biomarkers are often used as such tools for measuring the presence and severity of a disease. In this study, we examined two potential biomarkers in blood from patients with severe liver disease: peptidylglycine α-amidating monooxygenase (PAM) activity and bioactive adrenomedullin (bio-ADM). We examined whether these biomarkers are present in blood and in amounts associated with disease severity. We also tested if the diseased liver releases the biomarkers. We found that bio-ADM is increased in blood from patients with severe liver disease and that the liver itself releases bio-ADM to the bloodstream. For PAM activity, we also detected increased activity in blood associated with disease severity. In contrast, however, this biomarker was not shown to be released by the liver. Taken together, the two biomarkers may help to improve severe liver disease diagnosis and maybe allow for biochemical follow-up as the disease progresses.

Few complications after paracentesis in patients with cirrhosis and refractory ascites.

INTRODUCTION: The relevance of needle type and ultrasound guidance in connection with complications and technical problems in paracentesis in cirrhotic patients has only been sparsely described. The aim of this study was to evaluate paracentesis in cirrhotic patients with refractory ascites, focusing on technique, complications, amount of ascites drained and prognosis. MATERIAL AND METHODS: This was a retrospective study based on 51 cirrhotic patients with refractory ascites undergoing paracentesis. A total of 209 paracenteses were performed using a pigtail catheter and an intravenous catheter. Ultrasound-guided puncture or no ultrasound-guided punctured were compared with regard to amount of drained ascites, technical problems and complications both immediate and within a week of the procedure. The impact of coagulopathy was also investigated. RESULTS: 12% immediate and 5% late complications occurred, most of which were minor. No significant differences in the frequency of complications were found when comparing a pigtail to an intravenous catheter (8% versus 21%, OR = 2.81 95% CI (0.86; 9.13)), nor did the amount of drained ascites differ significantly. Ultrasound guidance did not significantly decrease the frequency of complications (7% versus 9%, OR 1.34 95% CI (0.37; 4.84)). Coagulopathy did not significantly affect the risk of complications. CONCLUSION: Paracentesis in patients with cirrhosis is associated with a low frequency of serious complications, regardless of the technique deployed. Although the material is of limited size, it appears that coagulopathy does not increase the risk of complications following this procedure.

Left atrial volume changes assessed by real time 3-dimensional echocardiography in relation to liver function and prognosis in patients with cirrhosis.

Left atrial enlargement is a known marker of chronic diastolic dysfunction and was recently shown to be an independent predictor of mortality in cirrhosis. Real time 3-dimensional echocardiography (3DE) is an emerging modality that enables accurate measurements of the left atrial (LA) volume and function. Assessment of LA volumes with 3DE has never been applied in cases of cirrhosis. We therefore aimed to investigate LA volumes using the novel 3DE technique in relation to liver dysfunction and outcome in patients with cirrhosis. A prospective study of 47 cirrhotic patients without cardiovascular disease and ten healthy controls. The patients underwent clinical evaluation, blood sampling, liver vein catheterization, ECG and tissue Doppler echocardiography, including 3DE. Patients were followed up for a median of 25 months with registration of death and liver transplantation (LT). 3DE-derived maximal left atrial volume index (LAVImax) and minimal left atrial volume index (LAVImin) were higher in patients with a Child Pugh score of 8 or higher than in patients with a score lower than 8 (30.0 vs. 22.3 mL/m2, P=0.008 and 14.6 vs. 9.5 mL/m2, P=0.04, respectively). LA volumes correlated with model for end-stage liver disease (MELD) score (r=0.40, P=0.005), hepatic venous pressure gradient (r=0.34, P=0.04), and biochemical markers of advanced liver disease. Twelve patients experienced the composite end-point of death or LT during follow-up and these patients had increased LA volumes with a higher LAVImax (34.3±14.8 vs. 25.9±7.3 mL/m2, P=0.01) and a higher LAVImin (16.3±7.3 vs. 10.8±5.1 mL/m2, P=0.007). Patients with advanced cirrhosis have increased minimal and maximal left atrial volumes, which correlate with the degree of the liver dysfunction and poor prognosis.

Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy.

BACKGROUND: Fibrogenesis and inflammation contribute to the progression of cirrhosis. However, it is unknown if these processes also contribute to the development of cirrhotic cardiomyopathy (CCM). Novel magnetic resonance imaging with quantification of the extracellular volume (ECV) provides an estimate of the fibrotic remodelling in the liver and heart. AIM: To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation. METHODS: A prospective study of 52 patients with cirrhosis and 14 healthy controls. All patients underwent contrast-enhanced MRI with T1-mapping and quantification of myocardial and liver ECV, biochemical assessments of collagen turnover (PRO-C3, PRO-C5, PRO-C6, collagen type IV degradation fragment, collagen type V degradation fragment, LG1M) and inflammation (TNFα, IL-1ß, IL-6, IL-8, IL-18, SDF1α, sCD163, sMR, soluble macrophage mannose receptor). RESULTS: Myocardial and liver ECV were increased in patients compared with healthy controls (myocardial ECV 31.2 ± 5.5% vs 27.4 ± 2.9%, P = 0.037; liver ECV 44.1 ± 9.6% vs 33.7 ± 6.7%, P < 0.001). Myocardial ECV correlated strongly with liver ECV (r = 0.48, P = 0.001) and biomarkers of collagen formation and inflammation (P < 0.005). Similarly, liver ECV correlated with biomarkers of collagen formation and inflammation (P < 0.003). In a multivariate analysis, liver ECV was predicted by biomarkers of collagen formation (PRO-C3 and PRO-C6), whereas myocardial ECV was predicted by biomarkers of collagen formation (PRO-C6) and inflammation (IL-6 and sMR). CONCLUSION: Structural myocardial changes seem closely related to liver fibrosis in patients with cirrhosis. The strong associations with biomarkers of collagen formation and inflammation provide new insight into the role of inflammation and fibrogenesis in the development of structural cardiac abnormalities, potentially leading to CCM.